Abstract
There is growing evidence that hepatitis-C virus (HCV) infection might cause peripheral neuropathy. We aimed to investigate the prevalence, clinical and electrophysiological features of sensory neuropathy in patients with cryoglobulin negative HCV infection. We studied 46 consecutive cryoglobulin negative HCV positive patients (24 of them with and 22 without neuropathic symptoms, NS) and compared to 28 age and gender matched controls. In all patients and controls, clinical neuropathy symptom (NSS) and neuropathy deficit scores (NDS) were assessed and standard nerve conduction velocity (SNCV) and pain related-evoked potentials (PREP) were recorded. Both, SNCV and PREP were abnormal in 13 NS positive patients (13/46, 28%). Abnormal PREP but normal SNCV were found in 5 (5/46, 11%) NS positive and in 2 NS negative patients (2/46, 4%). PREP abnormalities correlated positive with both clinical neuropathy scores (NSS r = 0.62; p < 0.001; NDS r = 0.57; p < 0.001), but not with the duration of the disease, current viral load, or the virus subtype. PREP abnormalities were more frequent (16/33, 48.5%) in HCV patients treated with interferon than in therapy naïve patients (4/13, 30.8%); the difference was, however, not significant. In our present study (1) all virus subtypes are capable of inducing neuropathy, (2) no differences were found between interferon therapy and treatment naive patients, (3) the prevalence of peripheral sensory neuropathy including small sensory fibers (20/46, 43.5%) is higher than previously reported and (4) we found that detection of HCV associated neuropathy depends on the evaluation method.
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Abbreviations
- CNAS:
-
Clinical neuropathy assessment score
- HCV:
-
Hepatitis-C virus
- LEP:
-
Laser evoked potentials
- NDS:
-
Neuropathy deficit score
- NSS:
-
Neuropathy symptom score
- NS:
-
Neuropathy symptoms
- PREP:
-
Pain related evoked potentials
- SFN:
-
Small-fiber neuropathy
- SNCV:
-
Standard nerve conduction velocity
References
Agostino R, Cruccu G, Romaniello A, Innocenti P, Inghilleri M, Manfredi M (2000) Dysfunction of small myelinated afferents in diabetic polyneuropathy, as assessed by laser evoked potentials. Clin Neurophysiol 111:270–276
Amato AA, Oaklander AL (2004) Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 16—2004. A 76-year-old woman with numbness and pain in the feet and legs. N Engl J Med 350:2181–2189
Apartis E, Leger JM, Musset L, Gugenheim M, Cacoub P, Lyon-Caen O, Pierrot-Deseilligny C, Hauw JJ, Bouche P (1996) Peripheral neuropathy associated with essential mixed cryoglobulinaemia: a role for hepatitis C virus infection? J Neurol Neurosurg Psychiatry 60:661–666
Boonyapisit K, Katirji B (2002) Severe exacerbation of hepatitis C-associated vasculitic neuropathy following treatment with interferon alpha: a case report and literature review. Muscle Nerve 25:909–913
Cacoub P, Renou C, Rosenthal E, Cohen P, Loury I, Loustaud-Ratti V, Yamamoto AM, Camproux AC, Hausfater P, Musset L, Veyssier P, Raguin G, Piette JC (2000) Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d’Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l’Hepatite C. Medicine (Baltimore) 79:47–56
Citro V, Milan G, Tripodi FS, Gennari A, Sorrentino P, Gallotta G, Postiglione A, Tarantino G (2007) Mental status impairment in patients with West Haven grade zero hepatic encephalopathy: the role of HCV infection. J Gastroenterol 42:79–82
Costa J, Resende C, de Carvalho M (2003) Motor-axonal polyneuropathy associated with hepatitis C virus. Eur J Neurol 10:183–185
David WS, Peine C, Schlesinger P, Smith SA (1996) Nonsystemic vasculitic mononeuropathy multiplex, cryoglobulinemia, and hepatitis C. Muscle Nerve 19:1596–1602
De Martino L, Sampaolo S, Tucci C, Ambrosone L, Budillon A, Migliaresi S, Di Iorio G (2003) Viral RNA in nerve tissues of patients with hepatitis C infection and peripheral neuropathy. Muscle Nerve 27:102–104
Dyck PJ, Sherman WR, Hallcher LM, Service FJ, O’Brien PC, Grina LA, Palumbo PJ, Swanson CJ (1980) Human diabetic endoneurial sorbitol, fructose, and myo-inositol related to sural nerve morphometry. Ann Neurol 8:590–596
Ferri C, Marzo E, Longombardo G, Lombardini F, La Civita L, Vanacore R, Liberati AM, Gerli R, Greco F, Moretti A et al (1993) Interferon-alpha in mixed cryoglobulinemia patients: a randomized, crossover-controlled trial. Blood 81:1132–1136
Fodor M, Nagy V, Berta A, Tornai I, Pfliegler G (2008) Hepatitis C virus presumably associated bilateral consecutive anterior ischemic optic neuropathy. Eur J Ophthalmol 18:313–315
Garcia-Larrea L, Peyron R, Laurent B, Mauguiere F (1997) Association and dissociation between laser-evoked potentials and pain perception. Neuroreport 8:3785–3789
Ghini M, Mascia MT, Gentilini M, Mussini C (1996) Treatment of cryoglobulinemic neuropathy with alpha-interferon. Neurology 46:588–589
Gorson KC, Herrmann DN, Thiagarajan R, Brannagan TH, Chin RL, Kinsella LJ, Ropper AH (2008) Non-length dependent small fibre neuropathy/ganglionopathy. J Neurol Neurosurg Psychiatry 79:163–169
Haslbeck M, Redaelli M, Parandeh-Shab F, Luft D, Neundörfer B, Stracke H, Ziegler D (2000) Diagnostik, Therapie und Verlaufskontrolle der sensomotorischen diabetischen Neuropathien. German Diabetes Association 42:30–31
Holland NR, Crawford TO, Hauer P, Cornblath DR, Griffin JW, McArthur JC (1998) Small-fiber sensory neuropathies: clinical course and neuropathology of idiopathic cases. Ann Neurol 44:47–59
Katsarava Z, Ayzenberg I, Sack F, Limmroth V, Diener HC, Kaube H (2006) A novel method of eliciting pain-related potentials by transcutaneous electrical stimulation. Headache 46:1511–1517
Katsarava Z, Yaldizli O, Voulkoudis C, Diener HC, Kaube H, Maschke M (2006) Pain related potentials by electrical stimulation of skin for detection of small-fiber neuropathy in HIV. J Neurol 253:1581–1584
Khella SL, Frost S, Hermann GA, Leventhal L, Whyatt S, Sajid MA, Scherer SS (1995) Hepatitis C infection, cryoglobulinemia, and vasculitic neuropathy. Treatment with interferon alfa: case report and literature review. Neurology 45:407–411
Koskinas J, Kilidireas C, Karandreas N, Kountouras D, Savvas S, Hadziyannis E, Archimandritis AJ (2007) Severe hepatitis C virus-related cryoglobulinaemic sensory-motor polyneuropathy treated with pegylated interferon-a2b and ribavirin: clinical, laboratory and neurophysiological study. Liver Int 27:414–420
Lidove O, Cacoub P, Hausfater P, Wechsler B, Frances C, Leger JM, Piette JC (1999) Cryoglobulinemia and hepatitis C: worsening of peripheral neuropathy after interferon alpha treatment. Gastroenterol Clin Biol 23:403–406
Maisonobe T, Leger JM, Musset L, Cacoub P (2002) Neurological manifestations in cryoglobulinemia. Rev Neurol (Paris) 158:920–924
Nemni R, Sanvito L, Quattrini A, Santuccio G, Camerlingo M, Canal N (2003) Peripheral neuropathy in hepatitis C virus infection with and without cryoglobulinaemia. J Neurol Neurosurg Psychiatry 74:1267–1271
Obermann M, Katsarava Z, Esser S, Sommer C, He L, Selter L, Yoon MS, Kaube H, Diener HC, Maschke M (2008) Correlation of epidermal nerve fiber density with pain-related evoked potentials in HIV neuropathy. Pain 138:79–86
Polydefkis M, Yiannoutsos CT, Cohen BA, Hollander H, Schifitto G, Clifford DB, Simpson DM, Katzenstein D, Shriver S, Hauer P, Brown A, Haidich AB, Moo L, McArthur JC (2002) Reduced intraepidermal nerve fiber density in HIV-associated sensory neuropathy. Neurology 58:115–119
Ripault MP, Borderie C, Dumas P, Vallat JM, Goujon JM, Brecheteau P, Beauchant M, Silvain C (1998) Peripheral neuropathies and chronic hepatitis C: a frequent association? Gastroenterol Clin Biol 22:891–896
Rossi P, Morano S, Serrao M, Gabriele A, Di Mario U, Morocutti C, Pozzessere G (2002) Pre-perceptual pain sensory responses (N1 component) in type I diabetes mellitus. NeuroReport 13:1009–1012
Santoro L, Manganelli F, Briani C, Giannini F, Benedetti L, Vitelli E, Mazzeo A, Beghi E (2006) Prevalence and characteristics of peripheral neuropathy in hepatitis C virus population. J Neurol Neurosurg Psychiatry 77:626–629
Stewart JD, Low PA, Fealey RD (1992) Distal small fiber neuropathy: results of tests of sweating and autonomic cardiovascular reflexes. Muscle Nerve 15:661–665
Tagliati M, Grinnell J, Godbold J, Simpson DM (1999) Peripheral nerve function in HIV infection: clinical, electrophysiologic, and laboratory findings. Arch Neurol 56:84–89
Valeriani M, Rambaud L, Mauguiere F (1996) Scalp topography and dipolar source modelling of potentials evoked by CO2 laser stimulation of the hand. Electroencephalogr Clin Neurophysiol 100:343–353
Young MJ, Boulton AJ, MacLeod AF, Williams DR, Sonksen PH (1993) A multicentre study of the prevalence of diabetic peripheral neuropathy in the United Kingdom hospital clinic population. Diabetologia 36:150–154
Zaltron S, Puoti M, Liberini P, Antonini L, Quinzanini M, Manni M, Forleo MA, Rossi S, Spinetti A, Zanini B, Carosi G (1998) High prevalence of peripheral neuropathy in hepatitis C virus infected patients with symptomatic and asymptomatic cryoglobulinaemia. Ital J Gastroenterol Hepatol 30:391–395
Conflict of interest
Dr. Katsarava has received research grants and honoraria from Allergan and Bayer, and is an advisory board member for Allergan. Headache research at the Department of Neurology in Essen is supported by the German Research Council (DFG), the German Ministry of Education and Research (BMBF), and the European Union. Prof. Diener received honoraria for participation in clinical trials, contribution to advisory boards, or oral presentations from Addex Pharma, Allergan, Almirall, AstraZeneca, Bayer Vital, Berlin Chemie, CoLucid, Bohringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Grunenthal, Janssen-Cilag, Lilly, La Roche, 3M Medica, Minster, MSD, Novartis, Johnson & Johnson, Pierre Fabre, Pfizer, Schaper and Brummer, Sanofi-Aventis, Weber & Weber. He also received financial support for research projects from Allergan, Almirall, AstraZeneca, Bayer, GlaxoSmithKline, Janssen-Cilag, and Pfizer. Dr. Yoon, Dr. Obermann, Ms. Dockweiler, Dr. Assert, Dr. Canbay, Dr. Haag, Dr. Gerken report no disclosures.
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Yoon, MS., Obermann, M., Dockweiler, C. et al. Sensory neuropathy in patients with cryoglobulin negative hepatitis-C infection. J Neurol 258, 80–88 (2011). https://doi.org/10.1007/s00415-010-5686-1
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DOI: https://doi.org/10.1007/s00415-010-5686-1